Systemic inflammation has been linked with cancer development, cancer cachexia and poor outcome. Advanced lung cancer inflammation index (ALI) was developed to assess degree of systemic inflammation at the time of diagnosis in metastatic non-small cell lung (NSCLC) cancer patients.
Jafri et al BMC Cancer 2013, 13:158 http://www.biomedcentral.com/1471-2407/13/158 RESEARCH ARTICLE Open Access Advance lung cancer inflammation index (ALI) at diagnosis is a prognostic marker in patients with metastatic non-small cell lung cancer (NSCLC): a retrospective review Syed H Jafri1,2*, Runhua Shi1,2 and Glenn Mills1,2 Abstract Background: Systemic inflammation has been linked with cancer development, cancer cachexia and poor outcome Advanced lung cancer inflammation index (ALI) was developed to assess degree of systemic inflammation at the time of diagnosis in metastatic non-small cell lung (NSCLC) cancer patients Methods: In a single institution retrospective review 173 patients with metastatic NSCLC diagnosed between Jan 2000 and June 30 2011 were included ALI was calculated as (BMI x Alb / NLR) where BMI = body mass index, Alb = serum albumin, NLR (neutrophil lymphocyte ratio, a marker of systemic inflammation) Patients were divided into low inflammation (ALI ≥ 18) and high inflammation (ALI < 18) groups Kaplan-Meier method was used to estimate progression free survival and overall survival Log-rank test were used to compare the survivals among various factors Multivariate Cox regression was used to perform survival analysis in order to estimate the hazards ratio for various factors Results: Among 173 patients median age was 57 years, 67% were male, 52% had adenocarcinoma Patients with an ALI score of < 18 suggesting high systemic inflammation were significantly more likely to have more than sites of metastatic disease, have poor performance status and less likely to receive any chemotherapy Their median progression free survival and overall survival was 2.4 months and 3.4 months as opposed to 5.1 months and 8.3 months in patients with ALI >18 (P < 0.001) On multi-variate analysis ALI score of 5 was shown to be an independent predictor of overall survivals [9] We wanted to evaluate if degree of systemic inflammation at the time of diagnosis in patients with advanced NSCLC can be a prognostic marker for outcome For this purpose we developed a simple index based on patient’s height, weight, serum albumin and NLR from the time of diagnosis We call this advanced lung cancer inflammation index (ALI) The purpose of this study was to see if advanced lung cancer inflammation index (ALI) at the time of diagnosis can predict survival outcomes in patients with newly diagnosed metastatic NSCLC Methods All patients diagnosed with stage IV NSCLC at our institution between Jan 2000 and Jun 30 2011 were screened for this retrospective review Patients with a prior history of non-small cell lung cancer presenting with relapse, prior history of other cancers in preceding years and those with incomplete medical information or follow up were excluded Height, weight, absolute neutrophil count, absolute lymphocyte count and serum albumin obtained from the medical records were recorded from the date of diagnosis or from the date closest to the date of diagnosis Most data points were from within weeks of the date of diagnosis and none were more than weeks after diagnosis Radiological response and date of progression were taken from the medical records as judged at that time by the treating physician Date of death was obtained from tumor registry and or from medical records Progression free survival was defined as the time period between date of diagnosis till radiological progression or deterioration in Page of performance status rendering patient ineligible for further treatment or death Overall survival was defined as the time period between date of diagnosis and the date of death or date of last contact if exact date of death is unavailable The study was conducted after obtaining approval from Louisiana state university-Shreveport institutional review board Statistical methods Clinical indicators were calculated as follows Student t test was used to compare means and Pearson Chi-square test or the Fisher’s exact test was used to compare proportion where appropriate Kaplan-Meier method was used to estimate progression free survival and median overall survival Log-rank test were used to compare the survivals among various factors Multivariate Cox regression was used to perform survival analysis in order to estimate the hazards ratio for various factors Advanced lung cancer inflammation index (ALI) The Area under a receiver operating characteristic (ROC) curve was used to identify the factors that could predict patient’s response to the treatment or not Ideally a survival event should be used in this ROC analysis, however 97.8% of patients are dead and only patients are alive, therefore responses to treatment or not was used in the ROC analysis The areas under ROC curves, c statistics, were 0.67, 0.61, 0.65, 0.70 and 0.74 for absolute neutrophil count, absolute lymphocyte count, serum albumin, BMI, and ALI respectively Therefore based on the highest value of area under ROC curve, ALI was used to predict responses or not to the treatment in the ROC analysis The single optimal cut point for ALI score is 18.4 in which the sensitivity and specificity is 77.3% and 63.9% This optimal point was selected by using the minimum distance between the point 100% sensitive and 100% specific and any point on the ROC curve Advance lung cancer inflammation index (ALI) was defined as follows: Advance lung cancer inflammation index ALI ị ẳ BMI ị Albị=NLR Where: Body mass index BMIị ẳ weight lbị=ẵheight inị2 703 Alb = serum albumin in g/dLNeutrophil lymphocyte ratios (NLR) = ANC/ALCANC: Absolute neutrophil countALC: Absolute lymphocyte count In this study, for simplicity the ALI score were dichotomized as < =18 and >18 in the respectively analysis All p-value < 0.05 were considered statistically significant The SAS system 9.3 (SAS institute Inc Gary, NC) was used to performed all the analyses Jafri et al BMC Cancer 2013, 13:158 http://www.biomedcentral.com/1471-2407/13/158 Page of Results A total of 173 patient records with complete medical information and follow up were included in the final analysis Patient’s characteristics are shown in Table Median age was 57 years old with (range from 34 to 88 years) Two thirds of patients were male African Americans constituted approximately half of our patient population which is consistent with demographics in the city The most common histology was adenocarcinoma (52%), followed by squamous cell (20%), poorly differentiated carcinoma (10%) and various other histologies as shown in Table Epidermal growth factor receptor (EGFR) mutation status was not available for most (75%) patients with adenocarcinoma as our cohort included patients from as early as 2000 Of those patients that had EGFR mutation information available it was found to be negative in 65%, positive in 9% and 26% of samples had insufficient material to test EGFR status (Table 3) Table Patient characteristics with advanced NSCLC N = 173 (%) Age (median, range) 57 (34–88) SEX Male 116 (67) Female 57 (33) RACE African American 90 (52) White 83 (48) Performance status (PS) 0-1 130 (76) 2-4 42 (24) Histology Adenocarcinoma 91 (52) Non-adenocarcinoma 82 (47) Number of metastatic sites 1-2 93 (54) >2 80 (46) Chemotherapy No chemo 59 (34) Any chemo 114 (66) Table NSCLC distribution by histology N = 173 (%) Adenocarcinoma 91 (52) Squamous cell 34 (20) Poorly differentiated 17 (10) Adeno-squamous 11 (6) Non-small cell cancer (3) Large cell carcinoma (3) Carcinoma (3) Bronchoalveolar (1) Squamous cell-Small cell (0.5) Mucoepidermoid (0.5) NSCLC: Non-small cell lung cancer Different sites of metastatic disease included lung, liver, brain, bones, adrenal glands, spleen and retroperitoneal lymph nodes and each was considered a separate metastatic site (54%) of patients had up to metastatic sites and the rest had more than At the time of diagnosis most patients (76%) had an ECOG performance status of 0–1 and 24% had PS or higher About a third (35%) of all patients could not receive any chemotherapy due to poor PS or co-morbid illnesses Median number of chemotherapy cycles was with a range of 0–24 cycles At first response assessment 23% had response to chemotherapy, 14% had stable disease and 23% had progression of disease and 40% had decline in PS making them ineligible for further chemotherapy Median progression free survival for the entire group was 3.7 months and overall survival was 5.1 months In order to get an estimate of ongoing systemic inflammation at the time of diagnosis we calculated ALI for each patient using the formula described above Range of ALI was 0.46-158.4.Patients were then divided around 50th percentile mark into two groups, those with ALI of < 18 (more inflammation) and those with ALI of ≥ 18 (less inflammation) Their characteristics are listed in Table There was no significant difference in age at diagnosis, sex and race and tumor histology between the two groups Compared to patients with ALI score of ≥ 18 patients with an ALI score of < 18 were significantly more likely to have more than sites of metastatic disease at the First response assessment Response to chemotherapy 41 (23) Stable disease 24 (14) Table EGFR mutation status of adenocarcinoma patients N = 91 (%) Progression 39 (23) Not available Decline in performance status 69 (40) Tested 23 (25) EGFR negative 15 (65) Survival (months) 68 (75) Median progression free survival 3.7 Insufficient material (26) Median overall survival 5.1 EGFR positive (9) NSCLC: Non-small cell lung cancer EGFR: Epidermal growth factor receptor Jafri et al BMC Cancer 2013, 13:158 http://www.biomedcentral.com/1471-2407/13/158 Page of Table Patient characteristics and outcome between those with advanced lung cancer inflammation index ALI score 18 (less inflammation) at the time of diagnosis Variable ALI < 18 (n = 83) (%) ALI ≥ 18 (n = 90) (%) Age (median) 56 58 0.26 (a) Male 57 (69) 59 (65) 0.74 (b) AA 42 (51) 48 (53) 0.76 (b) Adenocarcinoma 51 (61) 53 (59) 0.75 (b) PS 2-4 27 (32) 15 (17) 0.02 (b) No chemotherapy 41 (49) 18 (20) 2 metastatic sites 48 (58) 32 (35) 0.003 (b) Response to chemotherapy 15 (18%) 50 (56%)